Verapamil protein binding in patients and in normal subjects.

Verapamil plasma protein binding was studied in four groups of 12 subjects each: (1) normal subjects; (2) patients with moderate renal insufficiency and patients requiring dialysis; (3) patients 1 to 4 days after coronary artery surgery; and (4) patients undergoing cardiac catheterization. In normal subjects, plasma protein binding of verapamil was 89.6 +/- 0.17% and was concentration independent over a range of 35 to 1,557 ng/ml, which includes the usual clinical plasma range. In normal subjects, plasma protein binding of verapamil was not affected by addition of its major metabolite, norverapamil, in ratios of 1.2 to 26.3 (norverapamil/verapamil) or by the addition of 10 micrograms of warfarin. The plasma protein binding of verapamil was not altered in the postsurgical state or in the dialysis patients. Verapamil protein binding was initially lower in the cardiac catheterization patients (mean = 86.34 +/- 2.13%, p less than 0.001) than in normal subjects and was still lower (mean = 83.29 +/- 3.04%, p less than 0.02) after heparinization. There was also a small increase in binding in the patients with renal insufficiency (p less than 0.05). Plasma protein binding of verapamil in mongrel dogs (mean = 90.7%) was the same order. We found verapamil to be approximately 90% bound in man and dogs and not markedly changed by any of the conditions studied.